A Study to Assess Absolute Bioavailability (ABA) of Mobocertinib (TAK-788) and to Characterize Mass Balance, Pharmacokinetics (PK), Metabolism, and Excretion of Carbon-14 ([14C])-Mobocertinib in Male Healthy Participants

A Phase 1 Study to Assess Absolute Bioavailability of TAK-788 and to Characterize Mass Balance, Pharmacokinetics, Metabolism, and Excretion of [14C]-TAK-788 in Male Healthy Subjects

The purpose of this study is to determine:

Period 1 (ABA): ABA of mobocertinib following single microdose intravenous administration of 50 microgram (mcg) (approximately 2 microcurie [mcCi]) [14 C]-]-mobocertinib and single oral administration of 160 milligram (mg) mobocertinib.

Period 2 (absorption, distribution, metabolism, and elimination [ADME]): the mass balance and metabolic profile of mobocertinib in plasma, urine, and feces, to characterize the PK of mobocertinib and its metabolites (AP32960 and AP32914) in plasma, whole blood, and urine, and total radioactivity concentration equivalents in plasma and whole blood following a single oral administration of 160 mg (approximately 100 mcCi) [14C]-mobocertinib solution.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers
• Intervention / Treatment: Drug: Mobocertinib

Detailed Description

The drug being tested in this study is called mobocertinib. The study will determine ABA of mobocertinib following single microdose of 50 mcg [14C]-mobocertinib and single oral administration of 160 mg mobocertinib and will assess the mass balance and metabolic profile of mobocertinib in plasma, urine, and feces following a single oral administration of 160 mg [14C]-mobocertinib solution, and will characterize the PK of mobocertinib and its metabolites in plasma, whole blood, and urine, and total radioactivity concentration equivalents in plasma and whole blood following a single dose of 160 mg [14C]-mobocertinib.

The study will enroll approximately 6 participants. The study is designed to consist of 2 periods: Period 1 (ABA study period) and Period 2 (ADME study period). In Period 1, all participants will receive single unlabeled oral 160 mg dose of mobocertinib as capsules. At 3.75 hours post oral dosing, participants will receive 15-minute intravenous infusion of a microdose of 50 mcg (approximately 2mcCi) [14C]-mobocertinib. In Period 2, participants will receive single dose of 160 mg (approximately 100 mcCi) [14C]-mobocertinib as an oral solution.

This single center trial will be conducted in the United States. The overall time to participate in this study is approximately 65 days including screening period. Participants will be contacted approximately 30 days after the last dose of study drug for a follow-up assessment.

• Study Type: Interventional
• Enrollment (Actual): 7
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Nebraska
    • Lincoln, Nebraska, United States, 68502
      • Celerion

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 17 years to 53 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Continuous non smoker who has not used nicotine containing products for at least 20 years prior to the first dosing and throughout the study, based on subject self-reporting.
2. Body mass index greater than or equal to (>=)18 and less than (˂) 30.0 kilogram per square meter (kg/m^2) at screening.

Exclusion Criteria:

1. Is mentally or legally incapacitated or has significant emotional problems at the time of the screening visit or expected during the conduct of the study.
2. Has history or presence of alcoholism or drug abuse within the past 2 years prior to the first dosing.
3. Has positive urine drug or alcohol results at screening or first check in.
4. Estimated creatinine clearance < 80 milliliter per minute (mL/min) at screening.
5. Has tattoo(s) or scarring at or near the site of intravenous (IV) infusion or any other condition which may interfere with infusion site examination, in the opinion of the investigator.
6. Has infrequent bowel movements (less than approximately once per day) within 30 days prior to first dosing.
7. Has recent history of abnormal bowel movements, such as diarrhea, loose stools, or constipation, within 2 weeks of first dosing.
8. Has received radiolabeled substances or has been exposed to radiation sources within 12 months of first dosing or is likely to receive radiation exposure or radioisotopes within 12 months of first dosing such that participation in this study would increase their total exposure beyond the recommended levels considered safe (that is., weighted annual limit recommended by the Commission on Radiological Protection [ICRP] of 3000 millirem).
9. Donation of blood or significant blood loss within 56 days prior to the first dosing.
10. Plasma donation within 7 days prior to the first dosing.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Mobocertinib 160 mg and [14C]-Mobocertinib 50 mcg + [14C]-Mobocertinib 160 mg; Mobocertinib 160 mg, capsule, orally, once under fasted state, followed by [14C]-mobocertinib 50 mcg (approximately 2 microcurie [mcCi]), infusion, intravenously, once on Day 1 of Period 1, further followed by a washout period of 9 days, followed by [14C]-mobocertinib 160 mg (approximately 100 mcCi), solution, orally, once under fasted state on Day 1 of Period 2.

Drug: Mobocertinib; Mobocertinib capsule, [14C]-Mobocertinib intravenous infusion, [14C]-Mobocertinib oral solution.; Other Names: TAK-788

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Period 1: Percent Absolute Oral Bioavailability (%F) for Mobocertinib	Absolute bioavailability (F), defined as the fraction or percentage of the unchanged, orally administered dose that is systemically available, relative to the total dose administered intravenously. Percent Absolute Oral Bioavailability (%F) was calculated as dose of [14C]-mobocertinib intravenous in mg*AUC∞ of mobocertinib (oral)/dose of mobocertinib (oral)* AUC∞ of [14C]-mobocertinib (intravenous)*100.	Day 1 pre-dose and at multiple time points (up to 144 hours) post-dose
Period 2: Percentage of Total Radioactivity (Cum%Dose) Recovered in Urine Relative to the Administered Radioactive Dose		Day 1 pre-dose and at multiple time points (up to 240 hours) post-dose
Period 2: Percentage of Total Radioactivity (Cum%Dose) Recovered in Feces Relative to the Administered Radioactive Dose		Day 1 pre-dose and at multiple time points (up to 432 hours) post-dose
Period 2: Amount of Total Radioactivity Excreted in Urine (Ae[UR])		Day 1 pre-dose and at multiple time points (up to 240 hours) post-dose
Period 2: Amount of Total Radioactivity Excreted in Feces (Ae[Fe])		Day 1 pre-dose and at multiple time points (up to 432 hours) post-dose
Period 2: Percentage of Administered Radioactive Dose (%Dose) Excreted in Urine for Mobocertinib		Day 1: Pre-dose, 0-12 hours (hrs), 12-24 hrs, 24-48 hrs, 48-72 hrs, 72-96 hrs, 96-120 hrs, 120-144 hrs, 144-168 hrs, 168-192 hrs, 192-216 hrs, 216-240 hrs post-dose
Period 2: Percentage of Administered Radioactive Dose (%Dose) Excreted in Feces for Mobocertinib		Day 1: at Pre-dose, 0-24 hours (hrs), 24-48 hrs, 48-72 hrs, 72-96 hrs, 96-120 hrs, 120-144 hrs, 144-168 hrs, 168-192 hrs, 192-216 hrs, 216-240 hrs; 240-264 hrs, 264-288 hrs, 288-312 hrs, 213-408 hrs and 408-432 hrs
Period 2, Cmax: Maximum Observed Plasma and Whole Blood Concentration for Mobocertinib and Its Metabolites (AP32960 and AP32914)		Day 1 pre-dose and at multiple time points (up to 240 hours) post-dose
Period 2, Tmax: Time to Reach the Maximum Plasma and Whole Blood Concentration (Cmax) for Mobocertinib and Its Metabolites (AP32960 and AP32914)		Day 1 pre-dose and at multiple time points (up to 240 hours) post-dose
Period 2: t(1/2): Terminal Disposition Phase Half-life of Mobocertinib and Its Metabolites (AP32960 and AP32914) in Plasma and Whole Blood		Day 1 pre-dose and at multiple time points (up to 240 hours) post-dose
Period 2, AUC∞: Area Under the Plasma and Whole Blood Concentration-time Curve From Time 0 to Infinity for Mobocertinib and Its Metabolites (AP32960 and AP32914)		Day 1 pre-dose and at multiple time points (up to 240 hours) post-dose
Period 2, AUClast: Area Under the Plasma and Whole Blood Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for Mobocertinib and Its Metabolites (AP32960 and AP32914)		Day 1 pre-dose at multiple time points (up to 240 hours) post-dose
Period 2, AUCt: Area Under the Plasma and Whole Blood Concentration-time Curve From Time 0 to Time t for Mobocertinib and Its Metabolites (AP32960 and AP32914)		Day 1 pre-dose and at multiple time points (up to 240 hours) post-dose
Period 2, Cmax: Maximum Observed Plasma Radioactivity Concentration Equivalents for [14C]-Mobocertinib		Day 1 pre-dose at multiple time points (up to 240 hours) post-dose
Period 2, Cmax: Maximum Observed Whole Blood Radioactivity Concentration Equivalents for [14C]-Mobocertinib		Day 1 pre-dose at multiple time points (up to 240 hours) post-dose
Period 2, Tmax: Time to Reach the Maximum Plasma and Whole Blood Radioactivity Concentration (Cmax) Equivalents for [14C]-Mobocertinib		Day 1 pre-dose at multiple time points (up to 240 hours) post-dose
Period 2, t(1/2z): Terminal Disposition Phase Half-life of Plasma and Whole Blood Radioactivity Concentration Equivalents for [14C]-Mobocertinib		Day 1 pre-dose at multiple time points (up to 240 hours) post-dose
Period 2, AUC∞: Area Under the Plasma Radioactivity Concentration Equivalents-time Curve From Time 0 to Infinity for [14C]-Mobocertinib		Day 1 pre-dose and at multiple time points (up to 240 hours) post-dose
Period 2, AUC∞: Area Under the Whole Blood Radioactivity Concentration Equivalents-time Curve From Time 0 to Infinity for [14C]-Mobocertinib		Day 1 pre-dose and at multiple time points (up to 240 hours) post-dose
Period 2, AUClast: Area Under the Plasma Radioactivity Concentration Equivalents -Time Curve From Time 0 to Last Quantifiable Concentration for [14C]-Mobocertinib		Day 1 pre-dose and at multiple time points (up to 240 hours) post-dose
Period 2, AUClast: Area Under the Whole Blood Radioactivity Concentration Equivalents -Time Curve From Time 0 to Last Quantifiable Concentration for [14C]- Mobocertinib		Day 1 pre-dose and at multiple time points (up to 240 hours) post-dose
Period 2, AUCt : Area Under the Plasma Radioactivity Concentration Equivalents-time Curve From Time 0 to Time t for [14C]-Mobocertinib		Day 1 pre-dose and at multiple time points (up to 240 hours) post-dose
Period 2, AUCt : Area Under the Whole Blood Radioactivity Concentration Equivalents-time Curve From Time 0 to Time t for [14C]-Mobocertinib		Day 1 pre-dose and at multiple time points (up to 240 hours) post-dose
Period 2, Aet1-t2: Amount of Unchanged Drug Excreted in the Urine in Each Collection Interval From t1 to t2 for Mobocertinib and Its Metabolites (AP32960 and AP32914)		Day 1: at Pre-dose, 0-12 hours (hrs), 12-24 hrs, 24-48 hrs, 48-72 hrs, 72-96 hrs, 96-120 hrs, 120-144 hrs, 144-168 hrs, 168-192 hrs, 192-216 hrs and 216-240 hrs post dose
Period 2, CLR: Renal Clearance for Mobocertinib and Its Metabolites (AP32960 and AP32914)		Day 1 pre-dose and at multiple time points (up to 240 hours) post-dose
Period 2, Percentage Change of [14C]-Radioactivity in Whole Blood Relative to Plasma Over the Time for [14C]-Mobocertinib, (Whole Blood : Plasma Partitioning Ratio)		At 0.5 hours (hrs), 1 hr, 2 hrs, 3 hrs, 4 hrs, 5 hrs, 6 hrs, 8 hrs, 12 hrs, 24 hrs, 36 hrs, 48 hrs, 72 hrs, 96 hrs, 120 hrs, 144 hrs, 168 hrs, 192 hrs, 216 hrs and 240 hrs post-dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Period 1, Ceoi: Plasma Concentration at the End of Infusion for [14C]-Mobocertinib, and Its Metabolites ([14C]-AP32960 and [14C]-AP32914)		Day 1 pre-dose and at multiple time points (up to 144 hours) post-dose
Period 1, Cmax: Maximum Observed Plasma Concentration for Mobocertinib and Its Metabolites (AP32960 and AP32914) After Oral Administration		Day 1 pre-dose and at multiple time points (up to 144 hours) post-dose
Period 1, Cmax: Maximum Observed Plasma Concentration for [14C]-Mobocertinib and Its Metabolites ([14C]-AP32960 and [14C]-AP32914) After Intravenous Administration		Day 1 pre-dose and at multiple time points (up to 144 hours) post-dose
Period 1, Time to Reach the Maximum Plasma Concentration (Cmax) for Mobocertinib and Its Metabolites (AP32960 and AP32914) After Oral, and [14C]-Mobocertinib and Its Metabolites ([14C]-AP32960 and [14C]-AP32914) After Intravenous Administration	Data for mobocertinib and its metabolites (AP32960 and AP32914) is reported following the oral administration, and data for [14C]-mobocertinib and its metabolites ([14C]-AP32960 and [14C]-AP32914) is reported following intravenous administration.	Day 1 pre-dose and at multiple time points (up to 144 hours) post-dose
Period 1, AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for Mobocertinib and Its Metabolites (AP32960 and AP32914) After Oral Administration		Day 1 pre-dose and at multiple time points (up to 144 hours) post-dose
Period 1, AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for [14C]-Mobocertinib and Its Metabolites ( [14C]-AP32960 and [14C]-AP32914) After Intravenous Administration		Day 1 pre-dose and at multiple time points (up to 144 hours) post-dose
Period 1, AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to Last Quantifiable Concentration for Mobocertinib and Its Metabolites (AP32960 and AP32914) After Oral Administration		Day 1 pre-dose and at multiple time points (up to 144 hours) post-dose
Period 1, AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to Last Quantifiable Concentration for [14C]-Mobocertinib and Its Metabolites ([14C]-AP32960 and [14C]-AP32914) After Intravenous Administration		Day 1 pre-dose and at multiple time points (up to 144 hours) post-dose
Period 1, AUCt: Area Under the Plasma Concentration-time Curve From Time 0 to Time t for [14C]-Mobocertinib and Its Metabolites ([14C]-AP32960 and [14C]-AP32914) After Intravenous Administration		Day 1 pre-dose and at multiple time points (up to 144 hours) post-dose
Period 1, t(1/2):Terminal Disposition Phase Half-Life of Mobocertinib and Its Metabolites (AP32960 and AP32914) in Plasma After Oral, and [14C]-Mobocertinib and Its Metabolites ( [14C]-AP32960 and [14C]-AP32914) in Plasma After Intravenous Administration	Data for mobocertinib and its metabolites (AP32960 and AP32914) is reported following the oral administration, and data for [14C]-mobocertinib and its metabolites ([14C]-AP32960 and [14C]-AP32914) is reported following intravenous administration.	Day 1 pre-dose and at multiple time points (up to 144 hours) post-dose
Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs)		Baseline up to 30 days after last dose of study drug in Period 2 (Day 41)
Number of Participants With Clinically Significant Change From Baseline in 12-lead Electrocardiogram (ECG) Findings		Baseline up to 30 days after last dose of study drug in Period 2 (Day 41)
Number of Participants With Clinically Significant Change From Baseline in Vital Signs		Baseline up to 30 days after last dose of study drug in Period 2 (Day 41)
Number of Participants With Clinically Significant Change From Baseline in Laboratory Values		Baseline up to 30 days after last dose of study drug in Period 2 (Day 41)

Collaborators and Investigators

• Sponsor: Millennium Pharmaceuticals, Inc.
• Investigators: Study Director: Medical Director, Millennium Pharmaceuticals, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): January 22, 2019
• Primary Completion (Actual): March 11, 2019
• Study Completion (Actual): March 11, 2019

Study Registration Dates

• First Submitted: January 18, 2019
• First Submitted That Met QC Criteria: January 18, 2019
• First Posted (Actual): January 22, 2019

Study Record Updates

• Last Update Posted (Actual): February 12, 2024
• Last Update Submitted That Met QC Criteria: February 8, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: Drug Therapy
• Other Study ID Numbers: TAK-788-1002; U1111-1223-7593 (Other Identifier: WHO)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: De-identified individual participant data from this particular study will not be shared as there is a reasonable likelihood that individual patients could be re-identified (due to the limited number of study participants/study sites)
• IPD Sharing Access Criteria: IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/. For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Clinical Study Report (CSR)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No